RESUMEN
We demonstrate the development of a new atmospheric pressure-atomic layer deposition(AP-ALD) system to coat the inner walls of capillary columns for gas chromatography (GC). Unlike traditional ALD, this reactor operates at near-atmospheric pressure and addresses the challenges of depositing thin films inside capillaries, which include long pump down times, deposition in high-aspect-ratio materials, and temperature control. We show ALD of alumina in 5 and 12 m capillaries (0.53 mm ID) via sequential half reactions of trimethylaluminum and water. Our system yields pinhole-free, uniform thin films. It includes small witness chambers for witness silicon shards before and after the capillary. An engineering flow/transport analysis of the device is provided. Our ALD alumina thin films are characterized by spectroscopic ellipsometry (SE), X-ray photoelectron spectroscopy, transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy. Alumina film growth achieved is 1.4-1.5 Å/cycle, which is consistent with previously reported results. Film thickness measurements by SE on witness shards of silicon and by TEM at both ends of the capillary are in good agreement. A capillary column coated with alumina is used to separate different gases by GC, although the retention times of gases are essentially the same as with an untreated fused silica capillary. This successful deposition of ALD alumina in long capillaries opens the door for other possible ALD coatings, including hybrid organic-inorganic coatings, using the 450+ ALD precursors available today.
RESUMEN
We report the fabrication of 6-phenylhexylsilane derivatized, sputtered silicon, solid phase microextraction fibers that show parts per trillion detection limits for polyaromatic hydrocarbons, and negligible carry over and phase bleed. Their fabrication involves sputtering silicon on silica fibers under various conditions. Six different fibers were evaluated by generating three different thicknesses of sputtered silicon at two different throw distances, which altered the morphologies of the silicon surfaces. All of the fibers were coated with similar thicknesses of 6-phenylhexylsilane (ca. 2 nm). These fibers were characterized with multiple analytical techniques. The optimum fiber configuration was then used to analyze polyaromatic hydrocarbons via direct immersion, gas chromatography mass spectrometry. Our best fiber for the extraction of low molecular weight polyaromatic hydrocarbons in water had similar performance to that of a commercial fiber. However, our fiber demonstrated ca. 3 times the extraction efficiency for higher molecular weight polyaromatic hydrocarbons. In addition, it outperformed the commercial fiber by showing better linearity, repeatability, and detection limits. A method for analyzing polyaromatic hydrocarbons in baby formula was developed, which showed very good linearity (0.5-125 ppb), repeatability (2-26%), detection limits (0.12-0.81 ppb), and recoveries (103-135%). In addition, our fiber showed much less (negligible) carry over and phase bleed than the commercially available fibers.
Asunto(s)
Fórmulas Infantiles/química , Hidrocarburos Policíclicos Aromáticos/análisis , Microextracción en Fase Sólida/métodos , Agua/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Límite de Detección , Fibras Minerales/análisis , Silanos/análisis , Silicio/análisis , Contaminantes Químicos del Agua/análisis , Contaminación del Agua/análisisRESUMEN
We report the preparation of high performance, sputtered, polydimethylsiloxane (PDMS)-coated solid phase microextraction (SPME) fibers that show negligible carry-over and phase bleed. This process involves sputtering silicon onto silica fibers and functionalizing the resulting porous nanostructures with ultrathin films of vapor-deposited PDMS. Different thicknesses of silicon (0.25, 0.8, and 1.8 µm) and PDMS (8, 16, and 36 nm) were produced and their extraction efficiencies evaluated. The deposition of PDMS was confirmed by time-of-fight secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS), spectroscopic ellipsometry (SE), and contact angle goniometry on model, planar silicon substrates. These fibers were investigated using direct immersion SPME coupled with gas chromatography-mass spectrometry (GC-MS) analysis of a series of polycyclic aromatic hydrocarbons (PAHs), which are carcinogenic pollutants. The 1.8 µm thick silicon coating with 16 nm of PDMS (Si (1.8 µm)/PDMS (16 nm)) produced the best response among the combinations tested. Conditions for the extraction of PAHs with this fiber were optimized and its extraction performance was compared to that of a commercial 7 µm PDMS fiber. The linearity (1-110 µgL-1), repeatability (RSD%, n = 3) (17% ave.), and minimum detection limits (0.6-1.5 µgL-1) of the sputtered fibers were determined and found to be superior to the commercial 7 µm PDMS fiber in many respects. Carry-over and phase bleed from commercial PDMS-based SPME fibers are two of their major drawbacks, which decrease their lifetimes and usefulness. Minimal carry-over and phase bleed were observed for our sputtered PDMS-coated fibers. In particular, our fiber only shows 12% of the phase bleed of the comparable commercial fiber. In addition, it shows no carry-over for analytes with retention times greater than pyrene, and only 5% of the carry-over of the other analytes. Our fibers could be used for at least 300 injections without any significant loss of performance.
Asunto(s)
Dimetilpolisiloxanos/química , Silicio/química , Microextracción en Fase Sólida/métodos , Cromatografía de Gases y Espectrometría de Masas , Límite de Detección , Espectroscopía de Fotoelectrones , Hidrocarburos Policíclicos Aromáticos/análisis , Temperatura , Factores de Tiempo , Agua/química , Contaminantes Químicos del Agua/análisisRESUMEN
Although new targeted therapies, such as ibrutinib and idelalisib, have made a large impact on non-Hodgkin's lymphoma (NHL) patients, the disease is often fatal because patients are initially resistant to these targeted therapies, or because they eventually develop resistance. New drugs and treatments are necessary for these patients. One attractive approach is to inhibit multiple parallel pathways that drive the growth of these hematologic tumors, possibly prolonging the duration of the response and reducing resistance. Early clinical trials have tested this approach by dosing two drugs in combination in NHL patients. We discovered a single molecule, MDVN1003 (1-(5-amino-2,3-dihydro-1H-inden-2-yl)-3-(8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine), that inhibits Bruton's tyrosine kinase and phosphatidylinositol-3-kinase δ, two proteins regulated by the B cell receptor that drive the growth of many NHLs. In this report, we show that this dual inhibitor prevents the activation of B cells and inhibits the phosphorylation of protein kinase B and extracellular signal-regulated kinase 1/2, two downstream mediators that are important for this process. Additionally, MDVN1003 induces cell death in a B cell lymphoma cell line but not in an irrelevant erythroblast cell line. Importantly, we found that this orally bioavailable dual inhibitor reduced tumor growth in a B cell lymphoma xenograft model more effectively than either ibrutinib or idelalisib. Taken together, these results suggest that dual inhibition of these two key pathways by a single molecule could be a viable approach for treatment of NHL patients.
Asunto(s)
Linfocitos B/efectos de los fármacos , Linfoma de Células B/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Inhibidores de las Quinasa Fosfoinosítidos-3 , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Adenina/análogos & derivados , Agammaglobulinemia Tirosina Quinasa , Animales , Antineoplásicos/farmacología , Linfocitos B/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular , Humanos , Linfoma de Células B/metabolismo , Linfoma no Hodgkin/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Fosforilación/efectos de los fármacos , Piperidinas , Purinas/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Quinazolinonas/farmacología , Receptores de Antígenos de Linfocitos B/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
The aberrant activation of B-cells has been implicated in several types of cancers and hematological disorders. BTK and PI3Kδ are kinases responsible for B-cell signal transduction, and inhibitors of these enzymes have demonstrated clinical benefit in certain types of lymphoma. Simultaneous inhibition of these pathways could result in more robust responses or overcome resistance as observed in single agent use. We report a series of novel compounds that have low nanomolar potency against both BTK and PI3Kδ as well as acceptable PK properties that could be useful in the development of treatments against B-cell related diseases.
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Direct, regioselective and metal-free synthesis of fused N-heterocyclic iodides is reported. This regioselective C-H functionalization is mediated by tert-butylhydroperoxide (TBHP), via dual activation of molecular iodine and a heterocyclic substrate, resulting in the in situ generation of electrophilic iodine species (I(+)), and free radical(s) (t)BuOË or (t)BuOOË, driving the iodination reaction.
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Yodo/química , Quinolinas/síntesis química , terc-Butilhidroperóxido/química , Halogenación , Modelos QuímicosRESUMEN
Diabetic population is more than 245 million worldwide and expected to be b380 million by 2025. One of the main causes of increasing rate of diabetes is stress and tension in day-to-day life, disturbing the homeostasis of positive and negative emotions to initiate pathophysiology of stress-induced diabetes. In the present study, in Group A of 34 patients, a herbo-mineral compound containing Shuddha Shilajatu, Shuddha Guggulu, Vijayasara Ghana, Saptarangi Ghana, and Triphala Ghana was administered in the dose of 3 gm/day in three divided doses with luke-warm water before meal for the duration of 8 weeks, which significantly relieved symptoms (60.52%) like Prabhuta Mutrata (54.55%), Avila Mutrata (66.67%), Daurbalya (61.36%), Shrama (59.32%), etc. with fasting blood sugar (4.05%) and postprandial blood sugar (9.95%). In another series of 34 patients (Group B), where psychological health promoting drug Shankhapushpi was administered in the dose of 1.5 gm/day in three divided doses for 8 weeks along with herbo-mineral compound. The percentage relief was found to be more better on symptoms (71.13%) like Prabhuta Mutrata (76.92%), Avila Mutrata (83.33%), Daurbalya (75%), Shrama (70.37%), fasting blood sugar (18.04%) and postprandial blood sugar (27.75%). Group B showed better results on psychological parameters like disturbed Manasabhava (29.16%) and Brief Psychiatry Rating Scale (38.28%). The high significance of χ(2) (15.50) on overall effect of therapy indicated better results in group B.